Imaging of cationic multifunctional liposome-mediated delivery of COX-2 siRNA.
Liposomes are a useful means of delivering molecular targeting agents such as small interfering RNA (siRNA) to downregulate specific pathways important in cancer growth and progression. The ability to non-invasively image these carriers is important to ascertain their delivery within the tumor. As cyclooxygenase-2 (COX-2) is an important therapeutic target in cancer, we investigated loading COX-2-specific siRNA into cationic liposomes containing MR contrast agents for imaging delivery in cancer cells and tumors. COX-2 and GAPDH siRNA, as well as Magnevist or Feridex, were loaded directly into the liposomes. These lipoplexes were used for cell transfection of the poorly differentiated and highly metastatic breast cancer cell line MDA-MB-231. PEGylated liposomes loaded with Feridex and fluorescently labeled COX-2 siRNA were used for in vivo delivery of lipoplexes in MDA-MB-231 breast cancer xenografts in female SCID mice. Transient transfection assays demonstrated potent and specific downregulation of the COX-2 protein in cells in culture. Tail vein injections of PEGylated COX-2 lipoplexes resulted in intratumoral delivery of siRNA. Biodistribution studies showed significant localization in the lung, liver and kidney at 24 h. These data demonstrate the feasibility of liposomal-mediated delivery of COX-2-specific siRNA to downregulate COX-2 in cancer cells, and multi-modality imaging of the delivery of specific siRNA in tumors.
Mikhaylova
M
M
JHU ICMIC Program, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stasinopoulos
I
I
Kato
Y
Y
Artemov
D
D
Bhujwalla
Z M
ZM
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D002412:Cations; D045744:Cell Line, Tumor / Q000637:transplantation; D003287:Contrast Media / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003911:Dextrans; D015536:Down-Regulation; D016503:Drug Delivery Systems; D005260:Female; D052203:Ferrosoferric Oxide; D016650:Fluorescein-5-isothiocyanate / Q000032:analysis; D005456:Fluorescent Dyes / Q000032:analysis; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics*; D009942:Organometallic Compounds / Q000032:analysis; D010087:Oxides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D011092:Polyethylene Glycols; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014162:Transfection; D014183:Transplantation, Heterologous
D002412:Cations; D003287:Contrast Media; D003911:Dextrans; D005456:Fluorescent Dyes; D008081:Liposomes; D058185:Magnetite Nanoparticles; D009363:Neoplasm Proteins; D009942:Organometallic Compounds; D010087:Oxides; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D007501:Iron; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C065507:ferumoxides; D016650:Fluorescein-5-isothiocyanate; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide